Osteoclasts, which control osteolysis, are large multinucleated cells derived from hematopoietic cells that differentiate into monocytes/macrophages. Differentiation and maturation of osteoclast precursor cells into osteoclasts are controlled by osteoblasts/stromal cells on the bone surface area. An osteoclast differentiation factor (RANKL; receptor activator of NF-κB ligand) is a membrane-bound protein belonging to the family of tumor necrosis factors (TNFs) guided by bone resorption factors onto osteoblasts/stromal cells, and it is essential for osteoclast differentiation/maturation (see Non-Patent Documents 1 and 2). It has been known that RANKL is partially cleaved by metalloprotease in an extracellular region so as to result in soluble RANKL. In practice, soluble RANKL is known to induce in vitro differentiation of macrophage precursor cells such as myelocytes, spleen cells, precursor cells in the peripheral blood, cells of a macrophage cell line, and the like into osteoclasts when coexisting with M-CSF.
Meanwhile, conventional osteopenia models have been prepared by methods involving ovariectomy (see Non-Patent Documents 3 to 6), low-calcium diet (see Non-Patent Documents 7 and 8), neurectomy (see Non-Patent Document 9), immobilization via hindlimb suspension (see Non-Patent Document 10), and the like. In any case, it takes approximately 1 to 4 weeks to cause development of osteopenia. Therefore, it has been time-consuming to evaluate drugs such as bone resorption suppressants (e.g., bisphosphonate and Cathepsin K inhibitors) and osteogenesis promoters (e.g., parathyroid hormone (PTH)). In addition, in the above animal models, osteoclast activation is indirectly induced by estrogen depletion, an increase in PTH, and the like. Therefore, it has been difficult to demonstrate in which phase of osteopenia a drug can be evaluated as being effective in vivo.    Non-Patent Document 1: Yasuda et al., Proc Natl Acad Sci USA 95: 3597, 1998    Non-Patent Document 2: Lacey et al., Cell 93: 165, 1998    Non-Patent Document 3: Thompson et al., Bone 17(Suppl.): 5125, 1995    Non-Patent Document 4: Wronski et al., Calcif Tissue Int 42: 179, 1988    Non-Patent Document 5: Wronski et al., Endocrinology 123: 681, 1988    Non-Patent Document 6: Wronski et al., Calcif Tissue Int 45: 360, 1989    Non-Patent Document 7: de Winter et al., Calcif Tissue Res 17: 303, 1975    Non-Patent Document 8: Geusens et al., J Bone Miner Res 6: 791, 1991    Non-Patent Document 9: Wakley et al., Calcif Tissue Int 43, 383, 1988    Non-Patent Document 10: Globus et al., J Bone Miner Res 1: 191, 1986